Structural rearrangement of Neisseria meningitidis transferrin binding protein A (TbpA) prior to human transferrin protein (hTf) binding.
Structural rearrangement of Neisseria meningitidis transferrin binding protein A (TbpA) prior to human transferrin protein (hTf) binding.
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DOI：
10.3906/kim-2102-25
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发表时间：
2021
影响因子：
1.4
通讯作者：
Özbil M
中科院分区：
文献类型：
--
作者：
Duran GN;Özbil M
Gram-negative bacterium Neisseria meningitidis, responsible for human infectious disease meningitis, acquires the iron (Fe3+) ion needed for its survival from human transferrin protein (hTf). For this transport, transferrin binding proteins TbpA and TbpB are facilitated by the bacterium. The transfer cannot occur without TbpA, while the absence of TbpB only slows down the transfer. Thus, understanding the TbpA-hTf binding at the atomic level is crucial for the fight against bacterial meningitis infections. In this study, atomistic level of mechanism for TbpA-hTf binding is elucidated through 100 ns long all-atom classical MD simulations on free (uncomplexed) TbpA. TbpA protein underwent conformational change from ‘open’ state to ‘closed’ state, where two loop domains, loops 5 and 8, were very close to each other. This state clearly cannot accommodate hTf in the cleft between these two loops. Moreover, the helix finger domain, which might play a critical role in Fe3+ ion uptake, also shifted downwards leading to unfavorable Tbp-hTf binding. Results of this study indicated that TbpA must switch between ‘closed’ state to ‘open’ state, where loops 5 and 8 are far from each other creating a cleft for hTf binding. The atomistic level of understanding to conformational switch is crucial for TbpA-hTf complex inhibition strategies. Drug candidates can be designed to prevent this conformational switch, keeping TbpA locked in ‘closed’ state.
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影响因子：
2.9
作者：
Halbrooks, PJ;He, QY;Mason, AB
通讯作者：
Mason, AB
影响因子：
4.4
作者：
JORGENSEN, WL;CHANDRASEKHAR, J;KLEIN, ML
通讯作者：
KLEIN, ML
影响因子：
6.3
作者：
BERENDSEN, HJC;VANDERSPOEL, D;VANDRUNEN, R
通讯作者：
VANDRUNEN, R
DOI：
10.1007/s00249-011-0700-9
发表时间：
2011-07-01
影响因子：
2
作者：
Schmid, Nathan;Eichenberger, Andreas P.;van Gunsteren, Wilfred F.
通讯作者：
van Gunsteren, Wilfred F.
影响因子：
3.1
作者：
Cornelissen, CN;Anderson, JE;Sparling, PF
通讯作者：
Sparling, PF